Aim: To explore parents’ and adolescents’ motives for accepting/declining participation in the ALL2008 trials and adolescents’ involvement in the decision-making process. Background: Children and adolescents with acute lymphoblastic leukaemia treated on the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol were eligible for two randomizations testing 6-mercaptopurine treatment intensifications to improve efficacy and Asparaginase de-escalation to reduce toxicity. We recently reported that while adolescents favoured treatment reduction, parents of young children favoured treatment intensification. Design: A qualitative, exploratory study. Methods: A maximum variation sampling strategy was used. Five adolescents aged 12–17 years, six parents of adolescents and five parents of children aged 1–12 years were interviewed in the period March–May 2015. Data were analysed using content analysis. Findings: Adolescents and parents emphasized the importance of adolescents’ active participation in decisions regarding enrolment into clinical trials. A majority of adolescents were either final or collaborative decision-makers. Parents stated that in case of disagreement, they would overrule the adolescents’ decision. There were no differences between motivations of preferences held by parents of children or adolescents, respectively. Decisions were based on subjective values attributed to cure contra toxicity and individual preferences for either standard or experimental treatment. The possibility of a negative outcome induced fear of decisional regret and distress by the parents, yet they invested considerable trust in the physician's expertise. Conclusion: Our findings highlight the importance of adolescents’ active involvement in consent conferences. Research on management of disagreements between adolescents and parents in trial decisions is needed.